Original Article

Exp Neurobiol 2009; 18(1): 13-18

Published online June 30, 2009

© The Korean Society for Brain and Neural Sciences

Celecoxib Attenuates Kainic Acid-induced Neuronal Cell Death Through Suppression of Microglial c-Jun N-terminal Kinase Phosphorylation

Jong-Seon Byun1†, So-Young Cho1†, Song-In Kim1, Yong-Soo Kwon2, Seong-Ho Jeon2, Myong-Jo Kim3, Hee Jae Lee1, Sung-Soo Kim1 and Wanjoo Chun1*

1Department of Pharmacology, College of Medicine, 2College of Pharmacy, 3Division of Bio-resources Technology, Kangwon National University, Chunchon 700-701, Korea

Correspondence to: *To whom correspondence should be addressed.
First two anthors egually contributed to this work.
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In the present study, neuroprotective property of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and its underlying mechanism were examined in the animal model of kainic acid (KA)-induced excitotoxicity. KA, administered intracerebroventricularly (i.c.v.), induced marked neuronal cell death with concurrent microglial activation and subsequent induction of inducible nitric oxide synthase (iNOS) in the hippocampus. Histopathological analysis demonstrated that celecoxib (100 mg/kg), pre-treated 1 hr before or post-treated 2 hr after KA i.c.v. injection, significantly attenuated KA-induced death of pyramidal neurons in CA3 region. Celecoxib obviously suppressed KA-induced microglial activation and subsequent iNOS expression. KA- induced phosphorylation of c-Jun N-terminal kinases (JNK) was attenuated with celecoxib treatments. The results of the present study demonstrate that suppression of JNK phosphorylation by celecoxib contributes to its neuroprotective action against KA-induced excitotoxicity suggesting that celecoxib may be a potentially valuable in the treatment of acute brain pathologies associated with excitotoxic neuronal damage such as epilepsy, stroke, and traumatic brain injury.

Keywords: kainic acid, celecoxib, cyclooxygenase-2 (COX-2), iNOS, c-Jun N-terminal kinases (JNK), microglia, neuronal death